This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sivan, E. Articles by Kanety, H. Search for Related Content PubMed PubMed Citation Articles by Sivan, E. Articles by Kanety, H.

Adiponectin in Human Cord Blood: Relation to Fetal Birth Weight and Gender

Department of Obstetrics and Gynecology (E.Si., S.M.-T., E.Sc.), Institute of Endocrinology (C.P., Y.E., R.H., H.K.), Sheba Medical Center, Tel-Hashomer, Israel 52621; Sackler School of Medicine, Tel Aviv University, Tel Aviv Israel 69978 (E.Si., E.Sc.); and Faculty of Life Sciences (Y.E.), Bar-Ilan University, Ramat Gan, Israel 51905

Address all correspondence and requests for reprints to: Hannah Kanety, Ph.D., The Institute of Endocrinology, Sheba Medical Center, Tel-Hashomer, 52601 Israel. E-mail: hkanety{at}sheba.health.gov.il.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The aim of this study was to examine whether adiponectin is present in human fetal blood, to define its association with fetal birth weight, and to evaluate whether dynamic changes in adiponectin levels occur during the early neonatal period. Cord blood adiponectin levels were extremely high (71.0 ± 21.0 µg/ml; n = 51) compared with serum levels in children and adults and positively correlated with fetal birth weights (r = 0.4; P < 0.01). No significant differences in adiponectin levels were found between female and male neonates. In addition, there was no correlation between cord adiponectin levels and maternal body mass index, cord leptin, or insulin levels. Cord adiponectin levels were significantly higher compared with maternal levels at birth (61.1 ± 19.0 vs. 17.6 ± 4.9 µg/ml; P < 0.001; n = 17), and no correlation was found between cord and maternal adiponectin levels. There were no significant differences between adiponectin levels at birth and 4 d postpartum (61.1 ± 19.0 vs. 63.8 ± 22.0 µg/ml; n = 17). These findings indicate that adiponectin in cord blood is derived from fetal and not from placental or maternal tissues. The high adiponectin levels in newborns compared with adults may be due to lack of negative feedback on adiponectin production resulting from lack of adipocyte hypertrophy, low percentage of body fat, or a different distribution of fat depots in the newborns.

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
ADIPONECTIN IS A plasma protein that has been discovered a few years ago (1, 2, 3, 4). It is produced exclusively and abundantly in adipose tissue and circulates at relatively high (micrograms per milliliter) concentrations (1, 2, 3, 4, 5). Recent findings have indicated that adiponectin has antiatherogenic properties (6, 7, 8). Other studies have demonstrated that it has antiinflammatory effects like inhibition of endothelial NF-B signaling (8) and suppression of phagocytic activity and TNF- production in macrophages (9).

Adiponectin is a member of the growing group of adipose secreted proteins, sometimes described as adipocytokines. As opposed to other members in this group like leptin, TNF-, and IL-6, adiponectin plasma levels in obese subjects are, paradoxically, lower than in nonobese subjects (5). Consistent with these data, adiponectin gene transcription is decreased in adipocytes from obese subjects (10). Conversely, weight reduction in obese individuals is accompanied by an increase in plasma adiponectin concentrations (11, 12), suggesting that fat mass may exert a negative feedback on adiponectin production. Increasing evidence supports the notion that adiponectin is an important regulator of insulin sensitivity. In humans, an inverse relationship between insulin resistance and plasma adiponectin levels has been observed (13, 14). Furthermore, linkage studies have demonstrated a strong association between insulin resistance and a site at chromosome 3q27, where the adiponectin-encoding gene is located (15). Moreover, genetic variations in the adiponectin gene are associated with increased risk of type 2 diabetes (16). Finally, administration of adiponectin to normal or obese mice improved glucose tolerance and insulin sensitivity (17, 18, 19).

In addition to regulation of whole-body metabolism, numerous studies have explored the role of adipocytokines and particularly leptin in intrauterine growth. The findings that leptin is present in cord blood and its levels are positively correlated with the neonate’s birth weight (20, 21, 22), as well as the high levels of expression of both leptin and leptin receptors in the placenta and fetus, suggest that leptin plays a key role in fetal development (23, 24).

At the present, no information is available in respect to adiponectin in intrauterine growth. In this view the aim of the present study was to examine whether adiponectin is present in cord blood and to define the association between this protein and fetal birth weight, gender, leptin, and insulin. In addition, we have studied whether dynamic changes of adiponectin levels occur in healthy neonates during early neonatal life.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Subjects

The present study was comprised of two sub-studies.

Study 1. This study was designed to evaluate adiponectin levels in cord blood and to determine its relation to birth weight, gender, leptin, and insulin. Cord blood was obtained from 51 neonates at the time of delivery and before the separation of the placenta. Mean (±SD) maternal age, body mass index (BMI) and gestational week of delivery were 31.5 ± 5.3 yr, 28.0 ± 4.0 kg/m², and 39.5 ± 1.6, respectively. Gestational age at delivery was calculated according to the last menstrual period and confirmed by ultrasound examination during the first trimester or early second trimester. All women delivered at term except for three women that delivered between 34 and 36 completed weeks of gestation. All the mothers were healthy and their pregnancies were without complications such as gestational diabetes or pregnancy-induced hypertension. Thirty-eight (74.5%) neonates were born by normal vaginal delivery, four by vacuum extraction (7.8%), one by forceps extraction (1.9%), and eight by elective cesarean section (15.6%). The indications for cesarean section were either maternal request or history of previous cesarean section. Twenty-eight of the neonates were females (54.9%), and 23 (45.1%) were males. Mean birth weight of the newborns was 3269 ± 675 g. Birth weight percentiles were calculated according to published standards (25). Six of the neonates (11.7%) were above the 90th percentile defined as large for gestational age; all weighed more then 4000 g. Eight of the neonates (15.6%) were below the 10th percentile defined as small for gestational age; all weighed less then 2750 g. All neonates were normal and did not suffer from any complication.

Study 2. This study was designed to compare maternal and newborn adiponectin levels and to assess the alterations in newborns’ adiponectin levels during the first days after birth. Seventeen healthy newborns, delivered by cesarean section, and their mothers were included in the study; nine of the neonates were females, and eight were males. Mean birth weight was 3194 ± 519 g. Mean maternal age, BMI, and gestational week of delivery were 31.2 ± 4.0 yr, 28.2 ± 4.8 kg/m², and 39.3 ± 0.7, respectively. All women were healthy; none had pregestational or gestational diabetes in this or any previous pregnancies. The women were invited for elective cesarean section; the indications for the operation were maternal request, breech presentation, or previous cesarean section. All mothers had an uneventful operation and a postoperative period without complications. All neonates were healthy without any complication during and after delivery. Blood samples were obtained from the mothers 1 d before the operation. Immediately after the delivery of the newborn a blood sample was taken from the cord blood before the separation of the placenta. A second blood sample was taken from the newborns on the fourth day after birth.

The Ethical Committee of the Sheba Medical Center approved the protocols of both studies. Informed consent was obtained from all mothers before their inclusion in the study.

Adiponectin, leptin, and insulin measurements

Serum samples, obtained by centrifugation of cord blood or maternal and newborn venous blood, were immediately frozen and stored at -30 C until further analysis. Adiponectin and leptin were determined using RIA kits (Linco Research, Inc., St. Charles, MO). The sensitivity of the adiponectin assay was 1 ng/ml, and the interassay coefficient of variation (CV) ranged from 6.9–9.3%. The sensitivity of the leptin assay was 0.5 ng/ml, and the interassay CV ranged from 3–6%. Insulin was measured by a chemiluminiscent immunometric method (Immulite 2000, Diagnostic Products Corp., Los Angeles, CA). The sensitivity of the assay was 2 mU/liter, and the interassay CV ranged from 4–5%.

Statistical analysis

The data are expressed as means ± SD. Mean serum adiponectin concentrations and other measures of the groups were compared by Kruskal-Wallis one-way ANOVA on ranks. Pearson’s correlation coefficient was used to determine the relationship between continuous variables.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Adiponectin, leptin, and insulin levels in cord blood

As shown in Fig. 1A, adiponectin was detectable in the cord blood of all 51 neonates in concentrations ranging from 25–118 µg/ml. The mean and median levels were 71.0 ± 21.0 µg/ml and 70.0 µg/ml, respectively. Adiponectin levels were positively correlated with birth weights (r = 0.4; P < 0.01; Fig. 1A) but were not correlated with maternal BMI or cord leptin or insulin levels. Leptin was detectable in cord blood of all neonates in concentrations ranging from 1.3–41.0 ng/ml (Fig. 1B). The mean and median levels were 10.1 ± 7.8 ng/ml and 8.1 ng/ml, respectively. As previously demonstrated (20), there was a positive correlation between leptin levels and birth weights (r = 0.3; P < 0.03; Fig. 1B), maternal BMI (r = 0.3; P < 0.02), and cord insulin serum levels (r = 0.5; P < 0.001). Insulin levels in cord blood ranged from 2–39 mU/liter. The mean and median levels were 6.4 ± 6.5 mU/liter and 4.5 mU/liter, respectively. Cord insulin levels were positively correlated with maternal BMI (r = 0.3; P < 0.02). No correlation between cord insulin levels and birth weights was found.

View larger version (26K): [in this window] [in a new window]   FIG. 1. Correlation between cord adiponectin (A) and leptin (B) levels and birth weight in 51 healthy newborns. A, r = 0.4; P < 0.01. B, r = 0.3; P < 0.02.

Adiponectin and leptin were found to be gender-dependent in adults (5, 26) and children (27). When comparing the 28 female neonates to the 23 male neonates included in this study, no significant differences were found in cord serum levels of adiponectin, leptin, and insulin (Table 1) as well as in birth weights (Table 1) or maternal parameters (data not shown).

Previous studies have demonstrated that the high leptin levels in cord blood are due to both fetal and placental production (21, 23, 24). To get further insight into the origin of adiponectin in cord blood, its levels were evaluated in a second group of 17 neonates at birth and 4 d postpartum. In addition, cord blood and maternal adiponectin levels were compared in this group. As depicted in Fig. 2A, cord blood adiponectin levels were significantly higher compared with maternal adiponectin levels at birth (61.1 ± 19.0 vs. 17.6 ± 4.9 µg/ml; P < 0.001), and no correlation was found between cord blood and maternal adiponectin levels. In addition, no significant differences were found between adiponectin levels at birth and 4 d postpartum (61.1 ± 19.0 vs. 63.8 ± 22.0 µg/ml; Fig. 2A). In contrast, leptin levels at delivery were significantly lower in the newborns compared with their mothers (7.9 ± 7.7 vs. 30.9 ± 10.0 ng/ml; P < 0.001; Fig. 2B) and markedly declined 4 d after delivery (7.9 ± 7.7 vs. 2.1 ± 0.8 ng/ml; P < 0.01; Fig. 2B).

View larger version (25K): [in this window] [in a new window]   FIG. 2. Comparison of maternal and newborn (n = 17) adiponectin (A) and leptin (B) levels at delivery and 4 d postpartum. *, P < 0.001; **, P < 0.01.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

The source of adiponectin in cord blood is still unknown. Our findings suggest that it is derived mainly from fetal tissues and not from maternal or placental tissues. Several lines of evidence support this notion. First, no correlation was found between maternal adiponectin serum concentrations and adiponectin levels in cord blood. In addition, adiponectin levels in cord blood were significantly higher compared with maternal adiponectin levels. Therefore, the possibility that a facilitated transport of adiponectin from the maternal blood through the placenta is responsible for the high levels of the hormone in cord blood seems unlikely. The possibility that placental adiponectin synthesis, although not yet described, may contribute to the high levels of adiponectin in cord blood is not supported by our findings as well. Because the feto-placental unit is separated during birth, the removal of the placenta is expected to cause a fall in the levels of serum adiponectin after birth, assuming that the circulating half-life of this adipocytokine is in the range of several hours (29). However, when comparing adiponectin levels at birth and 4 d post delivery, no decline in adiponectin was observed (Fig. 2A). In contrast, the levels of leptin, known to be synthesized and secreted in the placenta (23, 24), declined rapidly and dramatically 4 d postpartum (Fig. 2B), in accordance with previous studies (30).

The mechanisms of regulating plasma adiponectin levels in the fetus are still not known. Adiponectin seems to be produced and secreted exclusively by adipocytes. However, an increase in fat mass leads to down-regulation of adiponectin (5), whereas body weight reduction in obese (11) as well as in normal-weight subjects (31) results in elevation of adiponectin concentrations, suggesting that fat mass may exert a negative feedback on adiponectin production. The lack of such negative feedback could contribute to hyperadiponectinemia in newborns. Indeed, the percentage of body fat is significantly lower in newborns (13%) compared with children or adults (25–30%) (32). Similarly, hyperadiponectinemia was found in anorectic patients whose percentage of fat mass is markedly decreased (33, 34). Several studies have demonstrated that adiponectin expression is reduced in hypertrophic adipocytes upon increase in triglyceride content (35, 36). Moreover, these studies have indicated that the levels of expression of adiponectin may be more closely related to adipocyte size than adipose tissue mass or body weight, although the mechanisms underlying the correlation between larger adipocytes and down-regulation of adiponectin were not elucidated. Based on these studies, and with the assumption that adiponectin in the fetus originates mainly from adipose tissue, an additional explanation for the extremely high levels of adiponectin in the cord blood might be the lack of adipocyte hypertrophy in newborns. Indeed, analysis of adipose tissue histology of fat cells in newborns demonstrated two populations of cells in the adipose tissue: small cells that do not contain fat and larger cells that contain fat but are small in their diameter compared with adult fat cells (37, 38). Thus, the hyperadiponectinemia in newborns may be due to lack of negative feedback exerted in the large adipocytes. Such a mechanism is supported by recent studies that have demonstrated a striking increase in adiponectin in normal and obese subjects upon treatment with peroxisome proliferator-activated receptor- agonists like troglitazone and rosiglitazone, which markedly increase the number of newly differentiated small adipocytes, in conjunction with body weight gain (29, 39). Thus, the low fat mass and the prevalence of small adipocytes in newborns’ adipose tissue may explain the extremely high levels of adiponectin in cord blood. Because both adiponectin (13, 14) and adipocyte hypertrophy (40) are negatively correlated with insulin resistance, we can speculate that the increased population of small adipocytes in fetal adipose tissue and the high levels of adiponectin may account for the high insulin sensitivity in newborns (41). Whether adiponectin plays an important role in insulin sensitivity in neonates like in adults remains to be determined. Finally, it is very well known that human infants possess, in addition to the energy-storing white adipose tissue, a specialized type of fat, the brown adipose tissue (BAT). Recently, the adiponectin gene was found to be highly expressed in BAT in rats and mice, and it is under strikingly different hormonal regulation than in white adipose tissue (42, 43). Additional studies are required to determine whether BAT adiponectin may contribute to the high levels observed in human cord blood.

Another interesting finding in this study is the positive correlation between adiponectin and neonatal birth weight. Our null hypothesis was that a negative correlation exists between adiponectin and birth weight based on the negative correlation between obesity and adiponectin, which is well established in adults (5, 11). However, we found a statistically significant positive correlation (r = 0.4; P < 0.01) between adiponectin and birth weight. This positive correlation is compatible with the suggestion that in newborns the adipose tissue is composed mainly from small newly differentiated adipocytes that lack the factors that are responsible for inhibition of adiponectin production. This situation is analogous to the increase in plasma adiponectin along with weight gain after rosiglitazone or troglitazone treatment, due to increased number of newly differentiated adipocytes (29, 39). In addition, recent studies have demonstrated that adiponectin secretion from omental but not from sc adipocytes is negatively correlated with BMI (44). As newborns, opposed to adults, have mainly sc adipose tissue, it is likely that the lack of negative correlation between adiponectin in cord blood and birth weight is due to the different distribution of adipose tissue depots in newborns compared with adults.

Adiponectin levels were found to be gender-dependent in adults (5, 26); therefore, we compared its levels between female and male neonates. We found no differences in adiponectin levels (P < 0.87) between the two groups. The difference between the sexes in adults may reflect an effect of the sex hormones (45, 46) or other mediators that are either inactive, subtle, or absent in newborns. We did not find a significant difference in leptin levels between female and male neonates, although the levels were higher in the female neonates. Previous studies have been controversial with regard to this finding (47, 48, 49, 50).

In summary, adiponectin is present in the cord blood of human fetuses at levels that are extensively higher than measured in children or adults. Because we are just beginning to understand the physiological role of adiponectin in adults, it is rather difficult to speculate what is the role of this protein in fetuses and neonates. Nevertheless, adiponectin may have additional roles in intrauterine development, as previously described for other adipocytokines like leptin (51, 52). Data concerning the source and the regulation of this protein in the fetus, its physiological role, and its putative role in pathological processes are yet to be clarified.

	Acknowledgments

 
We thank Prof. Avraham Karasik for critical review of this manuscript.

	Footnotes

 
This work is part of Y.E.’s M.Sc. thesis.

Abbreviations: BAT, Brown adipose tissue; BMI, body mass index; CV, coefficient of variation.

Received July 8, 2003.

Accepted September 5, 2003.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF 1995 A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270:26746–26749[Abstract/Free Full Text]
2. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K 1996 cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (adipose most abundant gene transcript 1). Biochem Biophys Res Commun 221:286–289[CrossRef][Medline]
3. Hu E, Liang P, Spiegelman BM 1996 AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 271:10697–10703[Abstract/Free Full Text]
4. Nakano Y, Tobe T, Choi-Miura NH, Mazda T, Tomita M 1996 Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem (Tokyo) 120:803–812[Abstract/Free Full Text]
5. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y 1999 Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79–83[CrossRef][Medline]
6. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y 1999 Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100:2473–2476[Abstract/Free Full Text]
7. Okamoto Y, Arita Y, Nishida M, Muraguchi M, Ouchi N, Takahashi M, Igura T, Inui Y, Kihara S, Nakamura T, Yamashita S, Miyagawa J, Funahashi T, Matsuzawa Y 2000 An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res 32:47–50[Medline]
8. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y 2000 Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-B signaling through a cAMP-dependent pathway. Circulation 102:1296–1301[Abstract/Free Full Text]
9. Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y 2000 Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96:1723–1732[Abstract/Free Full Text]
10. Statnick MA, Beavers LS, Conner LJ, Corominola H, Johnson D, Hammond CD, Rafaeloff-Phail R, Seng T, Suter TM, Sluka JP, Ravussin E, Gadski RA, Caro JF 2000 Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes. Int J Exp Diabetes Res 1:81–88[Medline]
11. Yang W-S, Lee W-J, Funahashi T, Tanaka S, Matsuzawa Y, Chao C-L, Chen C-L, Tai T-Y, Chuang L-M 2001 Weight reduction increases plasma levels of an adipose-derived antiinflammatory protein, adiponectin. J Clin Endocrinol Metab 86:3815–3819[Abstract/Free Full Text]
12. Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, Giugliano D 2003 Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. J Am Med Assoc 289:1799–1804[Abstract/Free Full Text]
13. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y 2000 Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599[Abstract/Free Full Text]
14. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA 2001 Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935[Abstract/Free Full Text]
15. Kissebah AH, Sonnenberg GE, Myklebust J, Goldstein M, Broman K, James RG, Marks JA, Krakower GR, Jacob HJ, Weber J, Martin L, Blangero J, Comuzzie AG 2000 Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci USA 97:14478–14483[Abstract/Free Full Text]
16. Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K, Yamauchi T, Otabe S, Okada T, Eto K, Kadowaki H, Hagura R, Akanuma Y, Yazaki Y, Nagai R, Taniyama M, Matsubara K, Yoda M, Nakano Y, Kimura S, Tomita M, Ito C, Froguel P, Kadowaki T 2002 Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 51:536–540[Abstract/Free Full Text]
17. Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF 2001 Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 98:2005–2010[Abstract/Free Full Text]
18. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T 2001 The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946[CrossRef][Medline]
19. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE 2001 The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7:947–953[CrossRef][Medline]
20. Sivan E, Lin WM, Homko CJ, Reece EA, Boden G 1997 Leptin is present in human cord blood. Diabetes 46:917–919[Abstract]
21. Schubring C, Kiess W, Englaro P, Rascher W, Dotsch J, Hanitsch S, Attanasio A, Blum WF 1997 Levels of leptin in maternal serum, amniotic fluid, and arterial and venous cord blood: relation to neonatal and placental weight. J Clin Endocrinol Metab 82:1480–1483[Abstract/Free Full Text]
22. Matsuda J, Yokota I, Iida M, Murakami T, Naito E, Ito M, Shima K, Kuroda Y 1997 Serum leptin concentration in cord blood: relationship to birth weight and gender. J Clin Endocrinol Metab 82:1642–1644[Abstract/Free Full Text]
23. Reitman ML, Bi S, Marcus-Samuels B, Gavrilova O 2001 Leptin and its role in pregnancy and fetal development: an overview. Biochem Soc Trans 29:68–72[CrossRef][Medline]
24. Hoggard N, Haggarty P, Thomas L, Lea RG 2001 Leptin expression in placental and fetal tissues: does leptin have a functional role? Biochem Soc Trans 29:57–63[CrossRef][Medline]
25. Battaglia FC, Lubchenco LO 1967 A practical classification of newborn infants by weight and gestational age. J Pediatr 71:159–163[CrossRef][Medline]
26. Yannakoulia M, Yiannakouris N, Bluher S, Matalas A-L, Klimis-Zacas D, Mantzoros CS 2003 Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans. J Clin Endocrinol Metab 88:1730–1736[Abstract/Free Full Text]
27. Nemet D, Wang P, Funahashi T, Matsuzawa Y, Tanaka S, Engelman L, Cooper DM 2003 Adipocytokines, body composition, and fitness in children. Pediatr Res 53:148–152[CrossRef][Medline]
28. Stefan N, Bunt JC, Salbe AD, Funahashi T, Matsuzawa Y, Tataranni PA 2002 Plasma adiponectin concentrations in children: relationships with obesity and insulinemia. J Clin Endocrinol Metab 87:4652–4656[Abstract/Free Full Text]
29. Yu JG, Javorschi S, Hevener AL, Kruszynska YT, Norman RA, Sinha M, Olefsky JM 2002 The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 51:2968–2974[Abstract/Free Full Text]
30. Schubring C, Siebler T, Kratzsch J, Englaro P, Blum WF, Triep K, Kiess W 1999 Leptin serum concentrations in healthy neonates within the first week of life: relation to insulin and growth hormone levels, skinfold thickness, body mass index and weight. Clin Endocrinol (Oxf) 51:199–204[CrossRef][Medline]
31. Havel PJ, Stanhope KL, Sinha M, Dubuc GR, Phinney SD, Gender differences in circulating adiponectin concentrations and in adiponectin responses to 7 d of energy restriction in normal weight men and women. Proc 62nd Annual Meeting of the American Diabetes Association, San Francisco, CA, 2002, p A454 (Abstract 1867-P)
32. Schmelzle HR, Fusch C 2002 Body fat in neonates and young infants: validation of skinfold thickness versus dual-energy x-ray absorptiometry. Am J Clin Nutr 76:1096–1100[Abstract/Free Full Text]
33. Delporte ML, Brichard SM, Hermans MP, Beguin C, Lambert M 2003 Hyperadiponectinaemia in anorexia nervosa. Clin Endocrinol (Oxf) 58:22–29[CrossRef][Medline]
34. Pannacciulli N, Vettor R, Milan G, Granzotto M, Catucci A, Federspil G, De Giacomo P, Giorgino R, De Pergola G 2003 Anorexia nervosa is characterized by increased adiponectin plasma levels and reduced nonoxidative glucose metabolism. J Clin Endocrinol Metab 88:1748–1752[Abstract/Free Full Text]
35. Yamauchi T, Kamon J, Waki H, Murakami K, Motojima K, Komeda K, Ide T, Kubota N, Terauchi Y, Tobe K, Miki H, Tsuchida A, Akanuma Y, Nagai R, Kimura S, Kadowaki T 2001 The mechanisms by which both heterozygous peroxisome proliferator-activated receptor (PPAR) deficiency and PPAR agonist improve insulin resistance. J Biol Chem 276:41245–41254[Abstract/Free Full Text]
36. Kamon J, Yamauchi T, Waki H, Uchida S, Ito C, Suzuki H, Masashi A, Takasawa K, Kubota N, Terauchi Y, Tobe K, Kadowaki H, Mechanism for the regulation of adiponectin expression. Proc 62nd Annual Meeting of the American Diabetes Association, San Francisco, CA, 2002, p A87 (Abstract 351-P)
37. Boulton T, Dunlop M, Court J 1978 The growth and development of fat cells in infancy. Pediatr Res 12:908–911[Medline]
38. Soriguer Escofet FJ, Esteva de Antonio I, Tinahones FJ, Pareja A 1996 Adipose tissue fatty acids and size and number of fat cells from birth to 9 years of age: a cross-sectional study in 96 boys. Metabolism 45:1395–1401[CrossRef][Medline]
39. Phillips SA, Ciaraldi TP, Kong APS, Bandukwala R, Aroda V, Carter L, Baxi S, Mudaliar SR, Henry RR 2003 Modulation of circulating and adipose tissue adiponectin levels by antidiabetic therapy. Diabetes 52:667–674[Abstract/Free Full Text]
40. Okuno A, Tamemoto H, Tobe K, Ueki K, Mori Y, Iwamoto K, Umesono K, Akanuma Y, Fujiwara T, Horikoshi H, Yazaki Y, Kadowaki T 1998 Troglitazone increases the number of small adipocytes without the change of white adipose tissue mass in obese Zucker rats. J Clin Invest 101:1354–1361[Medline]
41. Farrag HM, Nawrath LM, Healey JE, Dorcus EJ, Rapoza RE, Oh W, Cowett RM 1997 Persistent glucose production and greater peripheral sensitivity to insulin in the neonate vs. the adult. Am J Physiol 272:E86–E93
42. Zhang Y, Matheny M, Zolotukhin S, Tumer N, Scarpace PJ 2002 Regulation of adiponectin and leptin gene expression in white and brown adipose tissues: influence of ß3-adrenergic agonists, retinoic acid, leptin and fasting. Biochim Biophys Acta 1584:115–122[Medline]
43. Viengchareun S, Zennaro M-C, Pascual-Le Tallec L, Lombes M 2002 Brown adipocytes are novel sites of expression and regulation of adiponectin and resistin. FEBS Lett 532:345–350[CrossRef][Medline]
44. Motoshima H, Wu X, Sinha MK, Hardy VE, Rosato EL, Barbot DJ, Rosato FE, Goldstein BJ 2002 Differential regulation of adiponectin secretion from cultured human omental and subcutaneous adipocytes: effects of insulin and rosiglitazone. J Clin Endocrinol Metab 87:5662–5667[Abstract/Free Full Text]
45. Nishizawa H, Shimomura I, Kishida K, Maeda N, Kuriyama H, Nagaretani H, Matsuda M, Kondo H, Furuyama N, Kihara S, Nakamura T, Tochino Y, Funahashi T, Matsuzawa Y 2002 Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein. Diabetes 51:2734–2741[Abstract/Free Full Text]
46. Combs TP, Berg AH, Rajala MW, Klebanov S, Iyengar P, Jimenez-Chillaron JC, Patti ME, Klein SL, Weinstein RS, Scherer PE 2003 Sexual differentiation, pregnancy, calorie restriction, and aging affect the adipocyte-specific secretory protein adiponectin. Diabetes 52:268–276[Abstract/Free Full Text]
47. Helland IB, Reseland JE, Saugstad OD, Drevon CA 1998 Leptin levels in pregnant women and newborn infants: gender differences and reduction during the neonatal period. Pediatrics 101(3):E12
48. Ertl T, Funke S, Sarkany I, Szabo I, Rascher W, Blum WF, Sulyok E 1999 Postnatal changes of leptin levels in full-term and preterm neonates: their relation to intrauterine growth, gender and testosterone. Biol Neonate 75:167–176[CrossRef][Medline]
49. Maffeis C, Moghetti P, Vettor R, Lombardi AM, Vecchini S, Tato L 1999 Leptin concentration in newborns’ cord blood: relationship to gender and growth-regulating hormones. Int J Obes Relat Metab Disord 23:943–947[CrossRef][Medline]
50. Papadopoulou FG, Mamopoulos AM, Triantos A, Constantinidis TC, Papadimas J, Assimakopoulos EA, Koliakos G, Mamopoulos M 2000 Leptin levels in maternal and cord serum: relationship with fetal development and placental weight. J Matern Fetal Med 9:298–302[CrossRef][Medline]
51. Cioffi JA, Shafer AW, Zupancic TJ, Smith-Gbur J, Mikhail A, Platika D, Snodgrass HR 1996 Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction. Nat Med 2:585–589[CrossRef][Medline]
52. Bennett BD, Solar GP, Yuan JQ, Mathias J, Thomas GR, Matthews W 1996 A role for leptin and its cognate receptor in hematopoiesis. Curr Biol 6:1170–1180[CrossRef][Medline]

This article has been cited by other articles:

				G. A Martos-Moreno, V. Barrios, M. Saenz de Pipaon, J. Pozo, I. Dorronsoro, M. Martinez-Biarge, J. Quero, and J. Argente Influence of prematurity and growth restriction on the adipokine profile, IGF1, and ghrelin levels in cord blood: relationship with glucose metabolism Eur. J. Endocrinol., September 1, 2009; 161(3): 381 - 389. [Abstract] [Full Text] [PDF]

				S. Mazaki-Tovi, H. Kanety, C. Pariente, R. Hemi, Y. Yinon, A. Wiser, E. Schiff, and E. Sivan Adiponectin and Leptin Concentrations in Dichorionic Twins with Discordant and Concordant Growth J. Clin. Endocrinol. Metab., March 1, 2009; 94(3): 892 - 898. [Abstract] [Full Text] [PDF]

				D. D Briana and A. Malamitsi-Puchner Intrauterine growth restriction and adult disease: the role of adipocytokines Eur. J. Endocrinol., March 1, 2009; 160(3): 337 - 347. [Abstract] [Full Text] [PDF]

				C. S. Mantzoros, S. L. Rifas-Shiman, C. J. Williams, J. L. Fargnoli, T. Kelesidis, and M. W. Gillman Cord Blood Leptin and Adiponectin as Predictors of Adiposity in Children at 3 Years of Age: A Prospective Cohort Study Pediatrics, February 1, 2009; 123(2): 682 - 689. [Abstract] [Full Text] [PDF]

				H. Pinar, S. Basu, K. Hotmire, L. Laffineuse, L. Presley, M. Carpenter, P. M. Catalano, and S. Hauguel-de Mouzon High Molecular Mass Multimer Complexes and Vascular Expression Contribute to High Adiponectin in the Fetus J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2885 - 2890. [Abstract] [Full Text] [PDF]

				L. Ibanez, G. Sebastiani, A. Lopez-Bermejo, M. Diaz, M. D. Gomez-Roig, and F. de Zegher Gender Specificity of Body Adiposity and Circulating Adiponectin, Visfatin, Insulin, and Insulin Growth Factor-I at Term Birth: Relation to Prenatal Growth J. Clin. Endocrinol. Metab., July 1, 2008; 93(7): 2774 - 2778. [Abstract] [Full Text] [PDF]

				K. Takahashi, S. Yamaguchi, T. Shimoyama, H. Seki, K. Miyokawa, H. Katsuta, T. Tanaka, K. Yoshimoto, H. Ohno, S. Nagamatsu, et al. JNK- and I{kappa}B-dependent pathways regulate MCP-1 but not adiponectin release from artificially hypertrophied 3T3-L1 adipocytes preloaded with palmitate in vitro Am J Physiol Endocrinol Metab, May 1, 2008; 294(5): E898 - E909. [Abstract] [Full Text] [PDF]

				A Klamer, K Skogstrand, D M Hougaard, B Norgaard-Petersen, A Juul, and G Greisen Adiponectin levels measured in dried blood spot samples from neonates born small and appropriate for gestational age Eur. J. Endocrinol., August 1, 2007; 157(2): 189 - 194. [Abstract] [Full Text] [PDF]

				T. Siahanidou, H. Mandyla, G.-P. Papassotiriou, I. Papassotiriou, and G. Chrousos Circulating levels of adiponectin in preterm infants Arch. Dis. Child. Fetal Neonatal Ed., July 1, 2007; 92(4): F286 - F290. [Abstract] [Full Text] [PDF]

				R. H. Willemsen, M. van Dijk, Y. B. de Rijke, A. W. van Toorenenbergen, P. G. Mulder, and A. C. Hokken-Koelega Effect of Growth Hormone Therapy on Serum Adiponectin and Resistin Levels in Short, Small-for-Gestational-Age Children and Associations with Cardiovascular Risk Parameters J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 117 - 123. [Abstract] [Full Text] [PDF]

				K. Kadowaki, M. Waguri, I. Nakanishi, Y. Miyashita, M. Nakayama, N. Suehara, T. Funahashi, I. Shimomura, and T. Fujita Adiponectin Concentration in Umbilical Cord Serum Is Positively Associated with the Weight Ratio of Fetus to Placenta J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 5090 - 5094. [Abstract] [Full Text] [PDF]

				M. Weyermann, C. Beermann, H. Brenner, and D. Rothenbacher Adiponectin and Leptin in Maternal Serum, Cord Blood, and Breast Milk Clin. Chem., November 1, 2006; 52(11): 2095 - 2102. [Abstract] [Full Text] [PDF]

				G. G. Gosman, H. I. Katcher, and R. S. Legro Obesity and the role of gut and adipose hormones in female reproduction Hum. Reprod. Update, September 1, 2006; 12(5): 585 - 601. [Abstract] [Full Text] [PDF]

				N. Bansal, V. Charlton-Menys, P. Pemberton, P. McElduff, J. Oldroyd, A. Vyas, A. Koudsi, P. E. Clayton, J. K. Cruickshank, and P. N. Durrington Adiponectin in Umbilical Cord Blood Is Inversely Related to Low-Density Lipoprotein Cholesterol But Not Ethnicity J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2244 - 2249. [Abstract] [Full Text] [PDF]

				L. J Martin, J. G Woo, S. R Geraghty, M. Altaye, B. S Davidson, W. Banach, L. M Dolan, G. M Ruiz-Palacios, and A. L Morrow Adiponectin is present in human milk and is associated with maternal factors Am. J. Clinical Nutrition, May 1, 2006; 83(5): 1106 - 1111. [Abstract] [Full Text] [PDF]

				K. K. Ong, J. Frystyk, A. Flyvbjerg, C. J. Petry, the Avon Longitudinal Study of Parents and Childre, A. Ness, and D. B. Dunger Sex-Discordant Associations With Adiponectin Levels and Lipid Profiles in Children. Diabetes, May 1, 2006; 55(5): 1337 - 1341. [Abstract] [Full Text] [PDF]

				S. Corbetta, G. Bulfamante, D. Cortelazzi, V. Barresi, I. Cetin, G. Mantovani, S. Bondioni, P. Beck-Peccoz, and A. Spada Adiponectin Expression in Human Fetal Tissues during Mid- and Late Gestation J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2397 - 2402. [Abstract] [Full Text] [PDF]

				E. Kajantie, T. Hytinantti, P. Hovi, and S. Andersson Cord Plasma Adiponectin: A 20-Fold Rise between 24 Weeks Gestation and Term J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4031 - 4036. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sivan, E. Articles by Kanety, H. Search for Related Content PubMed PubMed Citation Articles by Sivan, E. Articles by Kanety, H.